Clinical Management of VHL Tumors - Systemic Agents for VHL | Medical Symposium 2024

In this video, three renowned physicians share their expertise on the latest developments in treating VHL disease. They focus on the efficacy, safety, and future directions of the systemic therapy called belzutifan (Welireg).
Speaker #1: Dr. Eric Jonasch presents data from the LITESPARK-004 clinical trial, which evaluated the effectiveness of belzutifan in patients with VHL disease. The study involved 61 patients and was primarily focused on the response of kidney tumors to the medication, but also collected data on its effect on central nervous system (CNS) hemangioblastomas, retinal hemangioblastomas, and pancreatic neuroendocrine tumors. Dr. Jonasch highlights that the objective response rate for kidney tumors increased from 49% to 67% over time, indicating that belzutifan is effective at reducing tumor size in most patients. Additionally, the medication showed positive results in shrinking CNS hemangioblastomas-with a 48% objective response rate, pancreatic neuroendocrine tumors, with an impressive 91% response rate, and also in retinal hemangioblastomas based on the preliminary data that has been collected on 18 total eyes (objective response rate has not yet been determined). Additionally, belzutifan has shown to still be highly effective in 79% of patients after 42 months of treatment. He emphasizes that while belzutifan is generally tolerable, not all patients respond, and some develop resistance over time. Dr. Jonasch emphasizes the need for larger real-world data sets to better understand the mechanisms of resistance to belzutifan and to explore combination therapies that could enhance the drug's efficacy.
Speaker #2: Dr. Ramaprasad Srinivasan discusses the side effects of belzutifan and their impact on patients' quality of life, stressing the importance of balancing treatment benefits with potential risks. He notes that VHL patients are often younger and lead active lives, making them less willing to tolerate side effects. The most common side effects of belzutifan are anemia and fatigue, which, while considered low-grade, can significantly affect daily activities over prolonged periods. Dr. Srinivasan underscores the need for individualized treatment plans, considering dose adjustments or intermittent therapy to minimize side effects. He highlights challenges such as determining the optimal timing to start therapy, deciding how long to continue treatment, and balancing the risk of resistance against the benefits of ongoing therapy. He advocates for patient input in treatment decisions to ensure that quality of life is maintained.
Speaker #3: Dr. Othon Iliopoulos focuses on the treatment of central nervous system (CNS) hemangioblastomas in VHL patients using belzutifan, advocating for its consideration as a first-line therapy. He explains that hemangioblastomas are the most common tumors in VHL disease and can be challenging to treat surgically due to their location in the brain and spinal cord. Dr. Iliopoulos details how belzutifan has shown significant efficacy in reducing both the solid and cystic components of these tumors. Patients have experienced rapid symptom relief, often within days of starting the medication, and early responses are often visible in imaging studies within six weeks. He provides clinical examples where patients avoided multiple surgeries due to tumor shrinkage from belzutifan. Dr. Iliopoulos proposes that belzutifan should be considered as a potential first-line treatment for hemangioblastomas and calls for clinical trials to explore optimal dosing strategies, such as continuous versus intermittent dosing, and the possibility of increasing doses for resistant cases. He emphasizes the need for further research to understand the cell of origin for hemangioblastomas and to develop animal models to study tumor biology and test new treatments. Dr. Iliopoulos highlights the importance of international collaboration in these research efforts.
These insights underscore the transformative potential of belzutifan in managing VHL disease. While the medication shows significant promise in reducing tumor size and improving patient outcomes, considerations around side effects, optimal dosing, and long-term management remain critical.